Decellularized kidney extracellular matrix-based hydrogels for renal tissue engineering.

Kidney regeneration is hindered by the limited pool of intrinsic reparative cells. Advanced therapies targeting renal regeneration have the potential to alleviate the clinical and financial burdens associated with kidney disease. Delivery systems for cells, extracellular vesicles, or growth factors aimed at enhancing regeneration can benefit from vehicles enabling targeted delivery and controlled release. Hydrogels, optimized to carry biological cargo while promoting regeneration, have emerged as promising candidates for this purpose. This study aims to develop a hydrogel from decellularized kidney extracellular matrix (DKECM) and explore its biocompatibility as a biomaterial for renal regeneration. The resulting hydrogel crosslinks with temperature and exhibits a high concentration of extracellular matrix. The decellularization process efficiently removes detergent residues, yielding a pathogen-free biomaterial that is non-hemolytic and devoid of α-gal epitope. Upon interaction with macrophages, the hydrogel induces differentiation into both pro-inflammatory and anti-inflammatory phenotypes, suggesting an adequate balance to promote biomaterial functionality in vivo. Renal progenitor cells encapsulated in the DKECM hydrogel demonstrate higher viability and proliferation than in commercial collagen-I hydrogels, while also expressing tubular cells and podocyte markers in long-term culture. Overall, the injectable biomaterial derived from porcine DKECM is anticipated to elicit minimal host reaction while fostering progenitor cell bioactivity, offering a potential avenue for enhancing renal regeneration in clinical settings. STATEMENT OF SIGNIFICANCE: The quest to improve treatments for kidney disease is crucial, given the challenges faced by patients on dialysis or waiting for transplants. Exciting new therapies combining biomaterials with cells can revolutionize kidney repair. In this study, researchers created a hydrogel from pig kidney. This gel could be used to deliver cells and other substances that help in kidney regeneration. Despite coming from pigs, it's safe for use in humans, with no harmful substances and reduced risk of immune reactions. Importantly, it promotes a balanced healing response in the body. This research not only advances our knowledge of kidney repair but also offers hope for more effective treatments for kidney diseases.

The genome of a steinernematid-associated Pseudomonas piscis bacterium encodes the biosynthesis of insect toxins.

Several species of soil-dwelling Steinernema nematodes are used in the biocontrol of crop pests, due to their natural capacity to kill diverse lepidopteran species. Although this insect-killing trait is known to be augmented by the nematodes' Xenorhabdus endosymbionts, the role of other steinernematid-associated bacterial genera in the nematode lifecycle remains unclear. This genomic study aimed to determine the potential of Pseudomonas piscis to contribute to the entomopathogenicity of its Steinernema host. Insect larvae were infected with three separate Steinernema cultures. From each of the three treatments, the prevalent bacteria in the haemocoel of cadavers, four days post-infection, were isolated. These three bacterial isolates were morphologically characterised. DNA was extracted from each of the three bacterial isolates and used for long-read genome sequencing and assembly. Assemblies were used to delineate species and identify genes that encode insect toxins, antimicrobials, and confer antibiotic resistance. We assembled three complete genomes. Through digital DNA-DNA hybridisation analyses, we ascertained that the haemocoels of insect cadavers previously infected with Steinernema sp. Kalro, Steinernema sp. 75, and Steinernema sp. 97 were dominated by Xenorhabdus griffiniae Kalro, Pseudomonas piscis 75, and X. griffiniae 97, respectively. X. griffiniae Kalro and X. griffiniae 97 formed a subspecies with other X. griffiniae symbionts of steinernematids from Kenya. P. piscis 75 phylogenetically clustered with pseudomonads that are characterised by high insecticidal activity. The P. piscis 75 genome encoded the production pathway of insect toxins such as orfamides and rhizoxins, antifungals such as pyrrolnitrin and pyoluteorin, and the broad-spectrum antimicrobial 2,4-diacetylphloroglucinol. The P. piscis 75 genome encoded resistance to over ten classes of antibiotics, including cationic lipopeptides. Steinernematid-associated P. piscis bacteria hence have the biosynthetic potential to contribute to nematode entomopathogenicity.

The crosstalk between DNA repair and immune responses.

In recent years, increasing evidence has highlighted the profound connection between DNA damage repair and the activation of immune responses. We spoke with researchers about their mechanistic interplays and the implications for cancer and other diseases.

Adverse effects of trazodone in dogs on primary hemostasis and electrocardiogram: A single-blinded placebo-controlled crossover study.

BACKGROUND: Trazodone is a serotonin antagonist/reuptake inhibitor medication commonly used for anxiety in dogs. Therapy with selective serotonin reuptake inhibitors in humans is associated with bleeding disorders and increased arrhythmogenesis. HYPOTHESIS/OBJECTIVES: To evaluate markers of primary hemostasis and corrected QT (cQT) interval in dogs before and after oral administration of standard dosages of trazodone or placebo. ANIMALS: Fifteen apparently healthy, client-owned dogs. METHODS: A single-blinded, randomized placebo-controlled crossover study was performed. Dogs were administered trazodone (5 to 7.5 mg/kg PO Q12h) or placebo. [Correction added after first online publication on 14 October 2023. In the abstract (methods) section (57.5 mg/kg PO Q12h) changed as (5 to 7.5 mg/kg PO Q12h).] Buccal mucosal bleeding time (BMBT), platelet count, platelet aggregation via Plateletworks, PFA-100 closure time and cQT interval were measured. A Shapiro-Wilk test was performed followed by either a paired t test or a Wilcoxon signed-rank test. RESULTS: No significant difference was detected in the BMBT, PFA-100 closure times, platelet counts, and cQT interval between trazodone or placebo. However, using Plateletworks, there was a significant decrease in platelet aggregation after administration of trazodone (95%; 81-97 vs 62%; 39-89, P = .002) and not placebo (95%; 81-97 vs 91%; 81-96, P = .21). CONCLUSIONS: It is unknown if this represents a clinically relevant change or if dogs with preexisting impairment in primary hemostasis or receiving higher dosages or longer durations of trazodone could have a more substantial change in hemostatic variables.

The effects of a nutritional packet (live yeast, vitamins C and B1, and electrolytes) offered to steers in a calf-fed system on growth performance, nutrient digestion, feeding behavior, carcass characteristics, and ruminal variables.

Effects of a nutritional packet strategically offered to calf-fed system steers on growth performance, nutrient digestibility, feeding behavior, ruminal variables, and carcass characteristics were evaluated. Angus crossbred steer-calves (N = 60; body weight [BW] = 234 ±â€…4 kg) were used in a randomized complete block design (block = BW) and stratified into two treatments: 1) control; and 2) 30 g/steer-daily (dry matter [DM] basis) of a nutritional packet containing (steer-daily basis): Live yeast (Saccharomyces cerevisiae; 1.7 × 1010 CFU), vitamin C (Ascorbic acid, 162 mg), vitamin B1 (thiamin hydrochloride, 400 mg), sodium chloride (2.4 g), and potassium chloride (2.4 g). Animals were offered (electronic feed-bunks [SmartFeed, C-Lock Inc., Rapid City, SD]), a steam-flaked corn-based finishing diet to ad libitum (individual intake), once daily for 233 d. Treatments were offered during the first and last 60 days on feed (DOF). The GLIMMIX procedure of SAS was used, with steer as the experimental unit, treatment and phase (for feeding behavior and digestibility) as fixed effects, and BW-block as a random effect. Steers offered the nutritional packet had 14% less (P < 0.01) intake and 18% greater (P = 0.01) feed efficiency during the initial 30 DOF. Intake (days 0 to 233) was 6% greater (P = 0.02) for steers offered the nutritional packet, while BW gain was not different (P ≥ 0.44). Greater (P = 0.02) dressing percent (61.1% vs. 62%) for steers offered the packet was observed, while other carcass variables were not different (P ≥ 0.33). Digestibility of DM, organic matter, and fiber were greater (P < 0.01) for steers offered the packet. Steers offered the packet spent 13% less time eating during the first 60 DOF, while during the last 60 DOF a 14% greater meal frequency and 12.3% smaller mean meal size (treatment × phase interaction, P < 0.02) were observed. Steers offered the packet had a reduced (P ≤ 0.01) mean meal duration during both phases. Regardless of treatment, a decreased rumination (P ≤ 0.03) and chewing (P ≤ 0.01) activities were observed for the last 60 DOF compared to the first 60 DOF. Ruminal papillae area was 30% greater (P = 0.02) and the total volatile fatty acid (VFA) tended (P = 0.09) to be greater for steers offered the nutritional packet. The nutritional packet offered to calf-fed steers improved feed efficiency during the initial 30 d after arrival, while inducing superior overall intake, nutrient digestibility, dressing percentage, ruminal papillae area, and total ruminal VFA.

Draft genomes, phylogenomic reconstruction and comparative genome analysis of three Xenorhabdus strains isolated from soil-dwelling nematodes in Kenya.

As a proven source of potent and selective antimicrobials, Xenorhabdus bacteria are important to an age plagued with difficult-to-treat microbial infections. Yet, only 27 species have been described to date. In this study, a novel Xenorhabdus species was discovered through genomic studies on three isolates from Kenyan soils. Soils in Western Kenya were surveyed for steinernematids and Steinernema isolates VH1 and BG5 were recovered from red volcanic loam soils from cultivated land in Vihiga and clay soils from riverine land in Bungoma respectively. From the two nematode isolates, Xenorhabdus sp. BG5 and Xenorhabdus sp. VH1 were isolated. The genomes of these two, plus that of X. griffiniae XN45 - this was previously isolated from Steinernema sp. scarpo that also originated from Kenyan soils - were sequenced and assembled. Nascent genome assemblies of the three isolates were of good quality with over 70 % of their proteome having known functions. These three isolates formed the X. griffiniae clade in a phylogenomic reconstruction of the genus. Their species were delineated using three overall genome relatedness indices: an unnamed species of the genus, Xenorhabdus sp. BG5, X. griffiniae VH1 and X. griffiniae XN45. A pangenome analysis of this clade revealed that over 70 % of species-specific genes encoded unknown functions. Transposases were linked to genomic islands in Xenorhabdus sp. BG5. Thus, overall genome-related indices sufficiently delineated species of two new Xenorhabdus isolates from Kenya, both of which were closely related to X. griffiniae . The functions encoded by most species-specific genes in the X. griffiniae clade remain unknown.

Rooftop water harvesting for managed aquifer recharge and flood mitigation in tropical cities: Towards a strategy of co-benefit evaluations in João Pessoa, northeast Brazil.

Intense urbanisation in many coastal areas has led to intensification of groundwater consumption, while reducing permeable areas and increasing the frequency and magnitude of flooding. Among the potential strategies to compensate for these adverse effects, which are expected to become worse as a result of climate change, rooftop rainwater harvesting (RWH) in combination with managed aquifer recharge (MAR), may be indicated. This work investigated the performance of different configurations of such a system, tested as a twofold sustainable stormwater and domestic water management tool in a tropical metropole (João Pessoa, Brazil). This area located over a sedimentary aquifer system illustrates the water security challenges of densely urbanised areas in southern cities. To that end, several configurations of rooftop catchments and storage volumes were evaluated, by simulating a MAR-RWH system connected to the regional unconfined aquifer (Barreiras Formation) through a 6″ diameter injection well. Rainfall-runoff-recharge processes and water balances were simulated using monitored high-temporal resolution rainfall data. The results showed that catchments ranging from 180 to 810 m2, connected to tanks from 0.5 to 30.0 m³, are the optimal solutions in terms of efficient rainwater retention and peak flow reduction. These solutions provided mean annual estimates of aquifer recharge between 57 and 255 m³/yr from 2004 to 2019. The results of this study highlight the opportunity for MAR schemes to reconcile stormwater management and water supply goals.

Protocol for isolation of microbiota-derived membrane vesicles from mouse blood and colon.

Bacterial membrane vesicles have emerged as gadgets allowing remote communication between the microbiota and distal host organs. Here we describe a protocol for enriching vesicles from serum and colon that could widely be adapted for other tissues. We detail pre-clearing of serum or colon fluids using 0.2-µm syringe filters and their concentration by centrifugal filter devices. We also describe vesicle isolation with qEV size exclusion columns and finally the concentration of isolated vesicle fractions for downstream analyses. For complete details on the use and execution of this protocol, please refer to Erttmann et al. (2022).1.

Longitudinal trends of systemic lupus erythematous hospitalizations in the United States: a two-decade population-based study.

BACKGROUND: Longitudinal data are limited on systemic lupus erythematosus (SLE) hospitalizations. We aim to study longitudinal trends of SLE hospitalizations in the last 2 decades in the United States (U.S). METHODS: Data were obtained from the National Inpatient Sample database (NIS). We performed a 21-year longitudinal trend analysis of NIS 1998-2018. We searched for hospitalizations for adult patients with a "principal" diagnosis of SLE (SLE flare group) and those with "any" diagnosis of SLE (all SLE hospitalization group) using ICD codes. All non-SLE hospitalizations for adult patients were used as the control. Multivariable logistic and linear regression were used appropriately to calculate adjusted p-trend for the outcomes of interest. RESULTS: Incidence of SLE flare hospitalization reduced from 4.1 to 3.2 per 100,000 U.S persons from 1998 to 2018 (adjusted p-trend < 0.0001). The proportion of all hospitalized patients with SLE admitted principally for SLE reduced from 11.3% in 1998 to 5.7% in 2018 (adjusted p-tend < 0.0001). The proportion of hospitalized blacks in the SLE flare and all SLE hospitalization groups increased from 37.7% and 26.9% in 1998 to 44.7% and 30.7% in 2018 respectively (adjusted p-trend < 0.0001). The proportion of hospitalized Hispanics and Asians disproportionally increased in SLE flare hospitalizations compared to the control group. CONCLUSION: The incidence of hospitalization for SLE flare has reduced in the last 2 decades in the U.S. The proportion of hospitalized patients with SLE admitted principally for SLE has reduced significantly over time. However, the burden of SLE hospitalizations among ethnic minorities has increased over time. Key Points • The incidence of hospitalization for SLE flare has reduced in the last 2 decades in the U.S. • The proportion of hospitalized patients with SLE admitted principally for SLE has reduced significantly over time. • The burden of SLE hospitalizations among ethnic minorities such as blacks has increased over time.

Implementation of Universal Newborn Hearing Screening in the Philippines: A survey of registered newborn hearing centers

Background@#Universal newborn hearing screening is mandated in the Philippines through the Universal Newborn Hearing Screening and Intervention Act of 2009 (RA 9709). Newborn hearing screening (NBHS) centers are required to perform screening tests, compile and submit data on screened newborns, and advise parents on the subsequent steps after NBHS.@*Objective@#The study aimed to conduct a survey of the implementation of the Universal Newborn Hearing Screening and Intervention Program (UNHSIP) in the different regions of the country; and assess the information technology (IT) capabilities of hearing centers.@*Methods@#Fifty-one NBHS centers across twelve regions were surveyed through on-site inspections in 2016. Data was gathered on the centers’ testing capability, staffing, access to specialists, use of local protocols, connectivity, and IT capabilities. @*Results@#All surveyed centers followed the recommended protocols of the Manual of Operations of the Universal Newborn Hearing Screening and Intervention Act of 2009 (RA 9709). Among the 12 regions visited, only five (41.67%) had Category C centers with confirmatory testing and early amplification services as recommended. Majority of facilities (96.1%) were staffed by trained and certified personnel. A small percentage had access to subspecialists such as clinical audiologists (39.2%) and speech-language pathologists (23.5%). All facilities had computer access, but only 58.8% had internet access. Majority (94.1%) of the centers visited were not using the recommended data submission methods, specifically the use of registry cards and the online registry. Only 27.5% of centers had data on newborns who underwent confirmatory testing or early intervention. @*Conclusion@#Facilities were found to be compliant to NBHS screening protocols and majority complied with certification requirements for staff; but were found to be non-compliant with use of registry cards or the online registry. Majority of centers were able to contact the parents of neonates who did not pass newborn screening, but had no system to track outcomes. Lack of confirmatory and early intervention services in identified areas emphasize the need for development of regional centers. It is recommended that measures to improve the utilization of the online registry are taken.

Genotoxin-producing Salmonella enterica induces tissue-specific types of DNA damage and DNA damage response outcomes.

Introduction: Typhoid toxin-expressing Salmonella enterica causes DNA damage in the intestinal mucosa in vivo, activating the DNA damage response (DDR) in the absence of inflammation. To understand whether the tissue microenvironment constrains the infection outcome, we compared the immune response and DDR patterns in the colon and liver of mice infected with a genotoxigenic strain or its isogenic control strain. Methods: In situ spatial transcriptomic and immunofluorescence have been used to assess DNA damage makers, activation of the DDR, innate immunity markers in a multiparametric analysis. Result: The presence of the typhoid toxin protected from colonic bacteria-induced inflammation, despite nuclear localization of p53, enhanced co-expression of type-I interferons (IfnbI) and the inflammasome sensor Aim2, both classic features of DNA-break-induced DDR activation. These effects were not observed in the livers of either infected group. Instead, in this tissue, the inflammatory response and DDR were associated with high oxidative stress-induced DNA damage. Conclusions: Our work highlights the relevance of the tissue microenvironment in enabling the typhoid toxin to suppress the host inflammatory response in vivo.

Emergency Department Utilization by Patients With Eating Disorders: A National Population-Based Study.

Background There is a scarcity of national United States (U.S) data on emergency department (ED) utilization by patients with eating disorders. This study aims to determine the most common reasons for ED visits of patients with eating disorders, as well as baseline characteristics of patients who present due to eating disorders. Methods We obtained data from the Nationwide Emergency Department Sample (NEDS), the largest all-payer ED database in the United States. Each ED visit in NEDS 2018 can have only one "principal" diagnosis, which is the main reason for the visit and up to 34 "secondary" diagnoses. We abstracted data for all ED visits with "any" diagnosis of an eating disorder, using the ICD-10 code "F50". We highlighted the 10 most common "principal" diagnoses based on the organ system involved and the 10 most specific "principal" diagnoses for all ED visits by patients with any diagnosis of eating disorder. We then highlighted baseline characteristics of ED visits with a "principal" diagnosis of an eating disorder. Results There were a total of 56,901 ED visits for patients with eating disorders in 2018. Among these, 7,979 had an eating disorder as the "principal" diagnosis. Patients who visited the ED principally for eating disorders were more likely to be young females and came from higher-income households; about a third were admitted with 22.1 million U.S. dollars in aggregate ED charges. Mental disorders, and injuries and poisoning were the most common principal diagnosis by organ system categories, while eating disorders, major depression disorder (MDD), hypokalemia, and dehydration are common specific reasons for ED visits among patients with eating disorders. Conclusions Eating disorders, and its medical complications and psychiatric comorbidities such as MDD are common reasons for ED visits among patients with eating disorders. Management of the underlying eating disorder and their psychiatric comorbidities through a multidisciplinary approach in the outpatient setting is invaluable in reducing ED utilization by these patients.

Biomimetic Surface Topography from the Rubus fruticosus Leaf as a Guidance of Angiogenesis in Tissue Engineering Applications.

The promotion of angiogenesis is a fundamental step for efficient organ/tissue reconstitution and replacement. Thus, several strategies to promote vascularization of scaffolds were studied to satisfy this unsolved clinical need. The interface between cells and substrates is a determinant for the success of tissue engineering (TE) strategies. Substrate's topography is reported to play a key role in influencing endothelial cell behavior, namely, on its proliferation, metabolic activity, morphology, migration, and secretion of cytokines and chemokines. Therefore, surface topography of the biomaterial-based grafts is a crucial property that is considered in the development of a new TE approach. Herein, we hypothesize that the surface of Rubus fruticosus leaf plays a crucial role in driving angiogenesis since its architecture resembles the vascular structures at a biologically relevant size scale. For this, we produced biomimetic polycaprolactone (PCL) membranes (BpMs) replicating the surface topography of a R. fruticosus leaf by replica molding and nanoimprint lithography. Our results showed an enhanced performance in terms of proliferation of the human endothelial cell line on top of the BpM. Moreover, an asymmetric cellular spatial distribution among the surface of the BpM was observed. These cells seem to have higher density for longer time periods in the region that replicates the leaf veins. Finally, we assess the angiogenic capacity through a chick chorioallantoic membrane assay, revealing that BpMs are more prone to support angiogenesis than flat PCL membranes. We strongly believe that this strategy can bring new insights into developing TE strategies with an enhanced performance in terms of the vascular integration between the host and the scaffolds implanted.

The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis.

The microbiota are vital for immune homeostasis and provide a competitive barrier to bacterial and fungal pathogens. Here, we investigated how gut commensals modulate systemic immunity and response to viral infection. Antibiotic suppression of the gut microbiota reduced systemic tonic type I interferon (IFN-I) and antiviral priming. The microbiota-driven tonic IFN-I-response was dependent on cGAS-STING but not on TLR signaling or direct host-bacteria interactions. Instead, membrane vesicles (MVs) from extracellular bacteria activated the cGAS-STING-IFN-I axis by delivering bacterial DNA into distal host cells. DNA-containing MVs from the gut microbiota were found in circulation and promoted the clearance of both DNA (herpes simplex virus type 1) and RNA (vesicular stomatitis virus) viruses in a cGAS-dependent manner. In summary, this study establishes an important role for the microbiota in peripheral cGAS-STING activation, which promotes host resistance to systemic viral infections. Moreover, it uncovers an underappreciated risk of antibiotic use during viral infections.

Genetic connectivity of trypanosomes between tsetse-infested and tsetse-free areas of Kenya.

The prevalence rates of trypanosomes, including those that require cyclical transmission by tsetse flies, are widely distributed in Africa. Trypanosoma brucei and Trypanosoma congolense are actively maintained in regions where there are no tsetse flies although at low frequencies. Whether this could be due to an independent evolutionary origin or multiple introduction of trypanosomes due to continuous movement of livestock between tsetse-free and -infested areas is not known. Thus, the aim of the study was to carry out microsatellite genotyping to explore intra-specific genetic diversity between T. (Trypanozoon), T. congolense and Trypanosoma vivax from the two regions: tsetse infested and tsetse free. Microsatellite genotyping showed geographical origin-based structuring among T. (Trypanozoon) isolates. There was a clear separation between isolates from the two regions signalling the potential of microsatellite markers as diagnostic markers for T. brucei and Trypanosoma evansi isolates. Trypanosoma vivax isolates also clustered largely based on the sampling location with a significant differentiation between the two locations. However, our results revealed that T. congolense isolates from Northern Kenya are not genetically separated from those from Coastal Kenya. Therefore, these isolates are likely introduced in the region through animal movement. Our results demonstrate the occurrence of both genetic connectivity as well as independent evolutionary origin, depending on the trypanosome species between the two ecologies.

"If Their Face Starts Turning Purple, You Are Probably Doing Something Wrong": Young Men's Experiences with Choking During Sex.

Choking/strangulation during sex has become prevalent in the United States. Yet, no qualitative research has addressed men's choking experiences. Through interviews with 21 young adult men, we examined the language men use to refer to choking, how they first learned about it, their experiences with choking, and consent and safety practices. Men learned about choking during adolescence from pornography, partners, friends, and mainstream media. They engaged in choking to be kinky, adventurous, and to please partners. While many enjoyed or felt neutral about choking, others were reluctant to choke or be choked. Safety and verbal/non-verbal consent practices varied widely.

Self-Persuasion: An Experimental Evaluation of a Sexual Aggression Preventive Intervention for U.S. College Men.

Grounded in the self-persuasion paradigm (an indirect persuasion approach, which places people in situations that motivate them to change their behavior), this study evaluated a brief, online intervention to reduce sexual aggression perpetration and increase prosocial bystander behaviors among heterosexual male college students (N = 241) in the United States. Students were randomly assigned to three conditions: (a) a self-persuasion intervention, (b) a social norms control condition, and (c) a control condition focusing on sense of belongingness. The self-persuasion intervention integrated three social psychological theoretical perspectives on attitudinal and behavioral change-cognitive dissonance (e.g., creating a personalized video message for incoming male college freshmen to explain the importance of consent in sexual contact), self-affirmation (e.g., reflecting on one's core values and how they are congruent with sexual consent), and personal relevance (e.g., writing about personally relevant reasons to always seek consent when having sexual contact). Participants in the self-persuasion condition reported greater prosocial bystander behaviors (e.g., intervening in situations to prevent sexual aggression) 6 months after the intervention as compared with those in the other two conditions; however, there were no significant difference in the rate of self-reported sexual aggression perpetration across conditions. The positive effect of the self-persuasion intervention on prosocial bystander behaviors was mediated by reduced self-perceived likelihood to commit sexual aggression and moderated by in-group solidarity with other college students. That is, the intervention had the most positive effect on prosocial bystander behaviors among participants with a lower sense of in-group solidarity. These findings are discussed in light of the promise of self-persuasion for future sexual aggression prevention work.

Nuclear AIM2-Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair.

Radiation is an essential preparative procedure for bone marrow (BM) transplantation and cancer treatment. The therapeutic efficacy of radiation and associated toxicity varies from patient to patient, making it difficult to prescribe an optimal patient-specific irradiation dose. The molecular determinants of radiation response remain unclear. AIM2-like receptors (ALRs) are key players in innate immunity and determine the course of infections, inflammatory diseases, senescence, and cancer. Here it is reported that mice lacking ALRs are resistant to irradiation-induced BM injury. It is shown that nuclear ALRs are inhibitors of DNA repair, thereby accelerate genome destabilization, micronuclei generation, and cell death, and that this novel function is uncoupled from their role in innate immunity. Mechanistically, ALRs bind to and interfere with chromatin decompaction vital for DNA repair. The finding uncovers ALRs as targets for new interventions against genotoxic tissue injury and as possible biomarkers for predicting the outcome of radio/chemotherapy.